Toxicity hematologic effects

The primary systemic targets of endosulfan toxicity in animals following dermal exposure are the liver and kidney. Adverse hematological effects have also been observed following dermal administration of endosulfan. No studies were located regarding musculoskeletal effects in humans or animals after dermal exposure to endosulfan. 

The dogs appeared in good condition throughout the study. No hematological effects were ascribed to diisopropyl methylphosphonate. The authors concluded that the ingestion of diisopropyl methylphosphonate produced no toxic effects at the concentrations that the dogs received over the 90-day period of the study. 

Target Organ Toxicity. This section focuses on mechanisms for sensitive health effects of major concern for lead—cardiovascular effects, hematological effects, and neurological effects, particularly in children. Bone is a major sink for lead, and there is some limited information regarding the effects of lead on bone and potential mechanisms of action. Renal effects occur at relatively high blood lead levels and evidence of renal carcinogenicity has been demonstrated only in animals mechanisms for these effects will be discussed briefly. 

Mycophenolate mofetil (CellCept) inhibits DNA and RNA synthesis and has been shown to have a specific lymphocyte antiproliferative effect. Although not FDA approved for this indication, oral mycophenolate mofetil appears effective in the treatment of moderate to severe plaque psoriasis. The usual dose is 500 mg orally four times a day, up to a maximum of 4 g/day. Common adverse effects include GI toxicity (diarrhea, nausea, vomiting), hematologic effects (anemia, neutropenia, thrombocytopenia), and viral and bacterial infections. Lymphoproliferative disease or lymphoma has been reported. 

The seeds of this transformation were sown some years ago. The first so-called atypical antipsychotic, clozapine (Clozaril), was devised in the 1960s. Clozapine was used widely in Europe until a series of deaths from a toxic hematological (blood) side effect called agranulocytosis occurred in the mid-1970s. Clozapine resurfaced in the 1980s and was approved for use (under strict guidelines) in the United States in 1990. Since that time, several other atypical antipsychotics have been approved, and others loom on the horizon. 

Developmental Toxicity. No studies have been located that reported developmental effects on the offspring of humans exposed to 1,4-dichlorobenzene via the inhalation, oral, or dermal routes. Only one human case report mentioned the potential developmental effects of ingesting 1,4-dichlorobenzene at 38 weeks of gestation. The mother developed hematological effects due to 1,4-dichlorobenzene consumption, but she did deliver a normal 4.3-kg female infant. Based on this one report, there appears to be little developmental toxicity of 1,4-dichlorobenzene in humans (Campbell and Davidson 1970) however, more information is clearly needed to confirm this observation in humans. 

Hematologic effects Aspirin interferes with hemostasis. Avoid use if patients have severe anemia, history of blood coagulation defects, or take anticoagulants. Long-term therapy To avoid potentially toxic concentrations, warn patients on long-term therapy not to take other salicylates (nonprescription analgesics, etc). Salicylism Salicylism may require dosage adjustment. 

Hematologic effects Sulfonamide-associated deaths, although rare, have occurred from hypersensitivity of the respiratory tract, Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. 

CNS toxicity occurs because isoniazid has structural similarities to pyridoxine (vitamin Be) and can inhibit its actions. This toxicity is dose-related and more common in slow acetylators. Manifestations include peripheral neuropathy, optic neuritis, ataxia, psychosis and seizures. The administration of pyridoxine to patients receiving INH does not interfere with the tuberculostatic action of INH but it prevents and can even reverse neuritis. Hematological effects include anaemia which is also responsive to pyridoxine. In some 20% of patients antinuclear antibodies can be detected but only in a minority of these patients drug-induced lupus erythematosus becomes manifest. 

Its adverse effects are dose dependent. Hematological effects include anaemia and leucopenia. Other effects are nausea, headache, myalgia, insomnia, and rarely, myopathy and hepatotoxicity. CNS toxicity can manifest itself as seizures, confusion... 

No studies were located regarding hematological effects in animals following inhalation exposure to silver or silver compounds. Despite the lack of supportive animal data, occupational exposure findings suggest that hematological effects are not a sensitive indicator of silver toxicity. 

Phenylbutazone, a pyrazolone derivative, rapidly gained favor after its introduction in 1949 for the treatment of rheumatic syndromes, but its toxicities—particularly the hematologic effects (including aplastic anemia)—have resulted in its withdrawal from the North American and most European markets. It is rarely used today. 

The above results demonstrated hematological effects in animals following CDD exposure however, the observed changes in the red and white blood cell counts were nonspecific and were probably due to the broad systemic toxicity of 2,3,7,8-TCDD rather than to a direct effect on the hematological system. 

Toxicity Acute, prolonged exposure in workplaces has caused a variety of health disorders in workers (e.g., erythema, edema, skin peeling, loss of appetite, muscle weakness, paresthesia, CNS depression, peripheral nerve disorders, skin and respiratory irritation, chemical pneumonia in children).7 In addition, rubber solvents, varnish, thinners, and petroleum spirits cause skin irritation, respiratory problems, and hematologic effects in workers all demand proper handling and chemical safety. 

---